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1.
Eur Urol ; 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32165065

RESUMO

BACKGROUND: The PURE-01 study (NCT02736266) evaluated the use of pembrolizumab before radical cystectomy (RC) in muscle-invasive bladder cancer (MIBC). OBJECTIVE: To evaluate the ability of molecular signatures to predict the pathological complete response (CR: ypT0N0) and progression-free survival (PFS) after pembrolizumab and RC. DESIGN, SETTING, AND PARTICIPANTS: We analyzed the expression data from patients with T2-4aN0M0 MIBC enrolled in the PURE-01 study (N=84) and from patients of a retrospective multicenter cohort treated with cisplatin-based neoadjuvant chemotherapy (NAC; N=140). INTERVENTION: Neoadjuvant pembrolizumab or NAC and RC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Immune signatures and molecular subtyping (The Cancer Genome Atlas, consensus model, and genomic subtyping classifier [GSC]) were evaluated in relation to CR and PFS. Multivariable logistic regression analyses for CR were used, adjusting for gender and clinical T stage. RESULTS AND LIMITATIONS: The Immune190 signature was significant for CR on multivariable logistic regression analyses (p= 0.02) in PURE-01, but not in the NAC cohort (p= 0.7). Hallmark signatures for interferon gamma (IFNγ; p= 0.004) and IFNα response (p= 0.006) were also associated with CR for PURE-01, but not for NAC (IFNγ: p= 0.9 and IFNα: p= 0.8). In PURE-01, 93% of patients with the highest Immune190 scores (>1st quartile) had 2-yr PFS versus 79% of those with lower scores; no difference was observed in NAC patients, as well as for the other hallmarks in both groups. The neuroendocrine-like subtype had the worst 2-yr PFS in all three subtyping models (33%) and the GSC claudin-low subtype had the best, with no recurrences in 2 yr. Basal subtypes (across classifications) with higher Immune190 scores showed 100% 2-yr PFS after pembrolizumab therapy (p = 0.04, compared with basal-Immune190 low). Statistical analyses are limited by the small number of events and short follow-up. CONCLUSIONS: Higher RNA-based immune signature scores were significantly associated with CR and numerically improved PFS outcomes after pembrolizumab, but not after NAC. These data emphasize that RNA profiling is a potential tool for personalizing neoadjuvant therapy selection. PATIENT SUMMARY: We used gene expression profiling to evaluate the association between immune gene expression and response to neoadjuvant immunotherapy, compared with standard chemotherapy, in patients with muscle-invasive bladder cancer (MIBC). We found a significant association between immune gene expression and response to pembrolizumab, but not chemotherapy. We conclude that gene expression profiling has the potential to guide personalized neoadjuvant therapy in MIBC.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32144050

RESUMO

BACKGROUND: Nonurothelial carcinoma (UC) malignancies have traditionally been considered to have a more aggressive clinical course, and little is known about their response to neoadjuvant therapy. We examined the effect of neoadjuvant chemotherapy (NAC) on a large population of patients with bladder cancer (BCa) with different histologic variants (HVs). PATIENTS AND METHODS: We relied on a retrospective, multicenter database of 2858 patients with BCa who had undergone radical cystectomy with or without NAC from 1990 to 2017. Pure and mixed HVs were grouped into 6 categories: squamous cell carcinoma (SCC; n = 283; 45%), other subtypes (n = 95; 15%), micropapillary (n = 85; 14%), adenocarcinoma (n = 65; 10%), small cell (n = 54; 8.6%), and sarcomatous (n = 47; 7.6%). Kaplan-Meier and Cox regression analyses were used to examine cancer-specific survival (CSS) according to the HV, using pure UC as the reference. Logistic regression models were used to examine the odds of clinical-to-pathologic downstaging after NAC according to the HV. RESULTS: Overall, we identified 2229 cases of pure UC and 629 cases of BCa with HVs at radical cystectomy. Of the 450 NAC-treated patients, only those patients with SCC (n = 44; 9.8%) had had worse CSS (median CSS, 33 vs. 116 months; P < .001) and higher mortality rates (hazard ratio, 2.1; P = .03) compared with those with pure UC (n = 328; 72.9%). The results of the analyses were also confirmed when the pure and mixed cases were considered separately. After adjusting for NAC, only SCC showed a lower rate of clinical-to-pathologic downstaging (odds ratio, 0.4; P = .03) compared with UC. CONCLUSIONS: SCC was the HV exhibiting the lowest effect of NAC in terms of activity and CSS. Compared with pure UC, SCC seemed to be insensitive to traditional NAC regimens.

4.
BJU Int ; 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32175663

RESUMO

OBJECTIVES: To identify predictors of poor overall survival (OS) among penile squamous-cell carcinoma (pSCC) patients with clinical inguinal lymphadenopathy (cN+) in order to define the best candidate for neoadjuvant chemotherapy (NAC). MATERIALS AND METHODS: Using an international, multicenter database of 924 pSCC patients, we identified 334 cN+ men with available clinical and follow-up data. Lymph node involvement was defined either by the presence of palpable inguinal node disease or by preoperative CT assessment. 18F-FDG-PET/CT-scan was performed based on clinical judgment of the treating physician. Regression-tree analysis generated a risk stratification tool for prediction of 24-month overall mortality (OM). Kaplan-Meier explored the OS benefit related to the use of NAC according to the regression-tree stratified sub-groups. RESULTS: Of all, 120 (35.9%), 152 (45.5%), and 62 (18.6%) harbored cN1, cN2, and cN3 disease. 18F-FDG-PET/CT was performed in 48 (14.4%) patients, and 16 (4.8%) had inguinal & pelvic nodal PET detection. Median OS was 107 months, with 24-month OS of 66%. At regression-tree analysis (area under the curve = 70%), patients with cN3 and cN2 with PET/CT-detected inguinal & pelvic nodal activity had the higher risk of 24-month OM (>50%). NAC was associated with improved 24-month OS rates (54% vs. 33%) only in this sub-group of patients (p=0.002), and it was also confirmed after multivariable adjustment (HR: 0.28, 95% CI: 0.13-0.62, p=0.002). CONCLUSION: pSCC patients with cN3 or cN2 and inguinal & pelvic 18F-FDG-PET/CT-scan detected disease exhibited higher 24-month OM rates according to our regression-tree model. Neoadjuvant chemotherapy was associated with improved OS only in these subgroups of patients. Our novel decision model may serve to stratify cN+ patients, and identify those who most likely will benefit from NAC prior to radical surgical resection.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32203071

RESUMO

BACKGROUND: To investigate the effect of frailty on short-term postoperative outcomes in patients with prostate cancer treated with radical prostatectomy (RP). METHODS: Within the National Inpatient Sample database, we identified 91,618 RP patients treated between 2008 and 2015. The Johns Hopkins Adjusted Clinical Groups frailty-defining indicator was applied, and we examined the rates of frailty over time, as well as its effect on overall complications, major complications, nonhome-based discharge, length of stay (LOS), and total hospital charges (THCs). Time trends and multivariable logistic, Poisson and linear regression models were applied. RESULTS: Overall, 12,185 (13.3%) patients were frail. Rates of frail patients increased over time (from 10.3 to 18.2%; p < 0.001). Frail patients had higher rates of overall complications (16.6 vs. 8.6%), major complications (4.9 vs. 2.6%), nonhome-based discharge (5.9 vs. 5%), longer LOS (2 vs. 1), and higher THCs ($37,186 vs. $35,241) (all p < 0.001). Moreover, frailty was an independent predictor of overall complications (OR: 1.95), major complications (OR: 1.76), nonhome-based discharge (OR: 1.20), longer LOS (RR: 1.19), and higher THCs (RR: $3160) (all p < 0.001). Of frail patients, 10,418 (85.5%) neither exhibited body mass index ≥ 30 nor Charlson comorbidity index ≥ 2. CONCLUSIONS: On average, every seventh RP patient is frail and that proportion is on the rise. Frail individuals are at higher risk of adverse short-term postoperative outcomes, that cannot be predicted by other risk factors, such as obesity or comorbidities.

8.
Urol Oncol ; 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32122729

RESUMO

BACKGROUND: Lymph node invasion (LNI) at nephrectomy is one of the most important predictors of mortality in patients with nonmetastatic renal cell carcinoma (RCC). We analyzed the effect of histology on lymph node metastases at nephrectomy and its effect on survival in a contemporary cohort of patients with nonmetastatic RCC. METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2015), we identified 100,060 patients with clear-cell, papillary, chromophobe, sarcomatoid, and collecting duct RCC, who underwent nephrectomy with or without lymph node dissection for nonmetastatic RCC. Logistic regression models, cumulative incidence plots, and competing-risks regression models were performed. RESULTS: Overall, 10,590 patients underwent lymph node dissection for nonmetastatic RCC. Of these, LNI was recorded in 52 (7.0%), 615 (8.7%), 282 (13.9%), 316 (25.1%), 129 (38.3%), 45 (71.4%) patients with chromophobe, clear-cell, nonotherwise specified RCC, papillary, sarcomatoid, and collecting duct RCC histological subtypes, respectively. In logistic regression models, relative to clear-cell, papillary Odds ratio (OR 3.9), sarcomatoid (OR 6.3), collecting duct (OR 14.6) but not chromophobe RCC (OR 0.9; P = 0.5) independently predicted LNI at surgery. Moreover, in competing-risks regression models, LNI increased the risk of CSM 1.8-fold for sarcomatoid, 3.6-fold for clear-cell, 4.1-fold for papillary, and 6.7-fold for chromophobe histological subtype. CONCLUSIONS: Histology is an independent predictor of increased risk of LNI at nephrectomy. Moreover, the effect of pathological nodal stage on survival differs according to different histology.

12.
Eur Radiol ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32052171

RESUMO

OBJECTIVES: To evaluate the agreement among readers with different expertise in detecting suspicious lesions at prostate multiparametric MRI using Prostate Imaging Reporting and Data System (PI-RADS) version 2.1. METHODS: We evaluated 200 consecutive biopsy-naïve or previously negative biopsy men who underwent MRI for clinically suspected prostate cancer (PCa) between May and September 2017. Of them, 132 patients underwent prostate biopsy. Seven radiologists (four dedicated uro-radiologists and three non-dedicated abdominal radiologists) reviewed and scored all MRI examinations according to PI-RADS v2.1. Agreement on index lesion detection was evaluated with Conger's k coefficient, agreement coefficient 1 (AC1), percentage of agreement (PA), and indexes of specific positive and negative agreement. Clinical and radiological features that may influence variability were evaluated. RESULTS: Agreement in index lesion detection among all readers was substantial (AC1 0.738; 95% CI 0.695-0.782); dedicated radiologists showed higher agreement compared with non-dedicated readers. Clinical and radiological parameters that positively influenced agreement were PSA density ≥ 0.15 ng/mL/cc, pre-MRI high risk for PCa, positivity threshold of PI-RADS score 4 + 5, PZ lesions, homogeneous signal intensity of the PZ, and subjectively easy interpretation of MRI. Positive specific agreement was significantly higher among dedicated readers, up to 93.4% (95% CI 90.7-95.4) in patients harboring csPCa. Agreement on absence of lesions was excellent for both dedicated and non-dedicated readers (respectively 85.1% [95% CI 78.4-92.3] and 82.0% [95% CI 77.2-90.1]). CONCLUSIONS: Agreement on index lesion detection among radiologists of various experiences is substantial to excellent using PI-RADS v2.1. Concordance on absence of lesions is excellent across readers' experience. KEY POINTS: • Agreement on index lesion detection among radiologists of various experiences is substantial to excellent using PI-RADS v2.1. • Concordance between experienced readers is higher than between less-experienced readers. • Concordance on absence of lesions is excellent across readers' experience.

13.
Eur Urol Focus ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32057739

RESUMO

We performed a post hoc analysis of data from phase 3 and 4 studies to evaluate the efficacy of silodosin 8mg in patients with severe lower urinary tract symptoms (LUTS) related to benign prostatic obstruction (BPO). The presence of two or more of the following criteria was adopted to define severity: total International Prostate Symptom Score (IPSS) 20-35, quality of life (QoL) score 5-6, maximum urinary flow <5ml/s or postvoid residual volume ≥100ml, and prostate volume ≥50ml. Mean improvements in total (8.1 vs 4.7), storage (3.1 vs 2.0), voiding (5.0 vs 2.7), and QoL (1.3 vs 0.7) IPSS scores were significantly greater for patients receiving silodosin compared to placebo (all p< 0.0001). Mean improvements in total, storage, voiding, and QoL IPSS scores were similar for the severe and not severe LUTS cohorts. In conclusion, silodosin significantly improves symptoms and QoL in all LUTS/BPO patients, including those with severe symptoms. PATIENT SUMMARY: Silodosin improves symptoms and quality of life for patients with severe lower urinary tract symptoms related to benign prostatic obstruction.

14.
Int Urol Nephrol ; 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32002746

RESUMO

PURPOSE: To design a dedicated risk calculator for patients with penile urethra stricture who are scheduled to urethroplasty that might be used to counsel patients according to their pre-operative risk of failure. METHODS: Patients treated with penile urethroplasty at our center (1994-2018) were included in the study. Patients received 1-stage or staged penile urethroplasty. Patients with failed hypospadias repair, lichen sclerosus or incomplete clinical records were excluded. Treatment failure was defined as any required postoperative instrumentation, including dilation. Univariable Cox regression identified predictors of post-operative treatment failure and Kaplan-Meier analysis plotted the failure-free survival rates according to such predictors. Multivariable Cox regression-based risk calculator was generated to predict the risk of treatment failure at 10 years after surgery. RESULTS: 261 patients met the inclusion criteria. Median follow-up was 113 months. Out of 216 patients, 201 (77%) were classified as success and 60 (23%) failures. Former smoker (hazard ratio [HR] 2.12, p = 0.025), instrumentation-derived stricture (HR 2.55, p = 0.006), and use of grafts (HR 1.83, p = 0.037) were predictors of treatment failure. Model-derived probabilities showed that the 10-year risk of treatment failure varied from 5.8 to 41.1% according to patient's characteristics. CONCLUSIONS: Long-term prognosis in patients who underwent penile urethroplasty is uncertain. To date, our risk-calculator represents the first tool that might help physicians to predict the risk of treatment failure at 10 years. According to our model, such risk is largely influenced by the etiology of the stricture, the use of graft, and patient's smoking habits.

16.
Minerva Urol Nefrol ; 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32083416

RESUMO

BACKGROUND: To examine the predictive value of neutrophil-to-lymphocyte ratio in localized prostate cancer for surgical pathology and recurrence in patients treated by radical prostatectomy. METHODS: We evaluated 1 258 patients treated by radical prostatectomy at San Raffaele Hospital between 2011 and 2017 and assessed the association between preoperative neutrophil-to-lymphocyte ratio and surgical pathology (advanced stage, grade group ≥4, nodal involvement, grade discordance between biopsy and surgical pathology) and biochemical recurrence. RESULTS: The preoperative neutrophil-to-lymphocyte ratio was not significantly associated with advanced stage (≥T3), International Society of Urological Pathology (ISUP) grade (≥4) or discordance. At multivariable analysis, patients with higher neutrophil-to-lymphocyte ratio had lower risk of nodal involvement at final pathology (odds ratio [OR]: 0.77; 95% confidence interval [CI]: 0.64, 0.92; P=0.005). The preoperative level of neutrophil-to-lymphocyte ratio was associated with biochemical recurrence on univariate analysis (OR: 0.81, 95% CI: 0.68, 0.96; P=0.017). Such a relationship was not significant at multivariable analysis adjusting for tumor severity (OR: 0.93, 95% CI: 0.79, 1.09; P=0.4). CONCLUSIONS: Neutrophil-to-lymphocyte ratio does not have clinical utility for the prediction of adverse pathology and biochemical recurrence. Further research should focus on its value for predicting regional lymph node metastasis.

17.
J Urol ; : 101097JU0000000000000800, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32068488

RESUMO

INTRODUCTION: The aim of the study was to compare 11C-Choline and 68Ga-PSMA in men undergoing SLND for nodal recurrent PCa. MATERIALS AND METHODS: The study included 641 patients who experienced PSA rise and nodal recurrence after radical prostatectomy and underwent SLND. Lymph node recurrence was documented by PET/CT scan using either 11C-Choline (n=407; 63%) or 68Ga-PSMA ligand (n=234; 37%). The outcome was underestimation of tumour burden (difference between number of positive nodes on final pathology and number of positive spots at PET/CT). Multivariable analysis tested the association between PET/CT tracer (11C-Choline vs. 68Ga-PSMA) and underestimation of tumour burden. RESULTS: Overall, the extent of underestimation of tumour burden was significantly higher in the 11C-Choline group compared to the 68Ga-PSMA (p<0.0001). This was confirmed on multivariable analysis (p=0.028). Repeating these analyses according to PSA, the underestimation of tumour burden was lower with 68Ga-PSMA only when the PSA was ≤1.5 ng/ml. Conversely, the underestimation of the two tracers became similar when PSA was >1.5 ng/ml. Furthermore, we evaluated the risk of underestimation by number of positive spots on PET/CT scan. The higher the number of positive spots the higher the underestimation of tumour burden regardless of the tracer used (p=0.2). CONCLUSIONS: PET/CT scan significantly underestimates the burden of PCa recurrence, regardless of the tracer used. 68Ga-PSMA was associated with a lower rate of underestimation in patients with a PSA below 1.5 ng/ml and a limited nodal tumour load. In all other men, there was no benefit from 68Ga-PSMA over 11C-Choline in assessing the extent of nodal recurrence.

18.
J Surg Oncol ; 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32107785

RESUMO

BACKGROUND AND OBJECTIVES: To examine the effect of conditional survival on 5-year cancer-specific survival (CSS) probability after radical nephroureterectomy (RNU) in a contemporary cohort of patients with non-metastatic urothelial carcinoma of the upper urinary tract (UTUC). METHODS: Within the Surveillance, Epidemiology and End Results database (2004-2015), 6826 patients were identified. Conditional 5-year CSS estimates were assessed after event-free follow-up duration. Multivariable Cox regression (MCR) models predicted cancer-specific mortality (CSM) according to event-free follow-up length. RESULTS: Overall, 956 (14.0%) were T1 low grade(LG)N0 , 1305 (19.1%) T1 high grade(HG)N0 , 1215 (17.8%) T2 N0 , 2249 (32.9%) T3 N0 and 1101 (16.1%) T4 N0 /Tany N1-3 . From baseline, 93.4% to 94.2% in T1 LGN0 provided 5-year CSS and, respectively, 86.2% to 95.3% in T1 HGN0 , 77.5% to 87.8% in T2 N0 , 63.0% to 91.1% in T3 N0 , and 38.8% to 88.2% in T4 N0 /Tany N1-3 . In MCR models, relative to T1 LGN0 , T1 HGN0 (Hazard ratio [HR] 1.7), T2 N0 (HR 3.0), T3 N0 (HR: 5.2), and T4 N0 /Tany N1-3 (HR 11.9) were independent predictors of higher CSM. Conditional HRs decreased to levels equivalent to T1 LGN0 at 3 years vs 5 years of event-free survival for T1 HGN0 and all other groups, respectively. CONCLUSIONS: A direct relationship exists between event-free follow-up and survival probability after RNU. From a clinical perspective, such survival estimates may have particular importance during preoperative counseling.

19.
Kidney Blood Press Res ; 45(2): 166-179, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31982867

RESUMO

INTRODUCTION: An accurate assessment of renal function is needed in the majority of clinical settings. Unfortunately, the most used estimated glomerular filtration rate (eGFR) formulas are affected by significant errors in comparison to gold standards methods of measured GFR (mGFR). OBJECTIVE: The objective of the study is to determine the extent of the error of eGFR formulas compared to the mGFR in different specific clinical settings. METHODS: A total retrospectively consecutive cohort of 1,320 patients (pts) enrolled in 2 different European Hospitals (Center 1: 470 pts; Center 2: 850 pts) was collected in order to compare the most common eGFR formulas used by physicians with the most widespread mGFR methods in daily clinical practice (Iohexol Plasma Clearance -Center 1 [mGFR-iox] and Renal Scintigraphy -Center 2 [mGFR-scnt]). The study cohort was composed by urological, oncological, and nephrological pts. The agreement between eGFR and mGFR was evaluated using bias (as median of difference), precision (as interquartile range of difference) accuracy (as P30), and total deviation index. RESULTS: The most accurate eGFR formula in the comparison with gold standard method (Iohexol plasma clearance) in Center 1 was represented by s-creatinine and cystatin C combined Chronic Kidney Disease-Epidemiology Collaboration-cr-cy, even though the P30 is reduced (84%) under the threshold of 60 mL/min/1.73 m2. Similar results were found in Center 2, with a wider discrepancy between mGFR-scnt and eGFR formulas due to the minor accuracy of the nuclear tool in respect to the mGFR-iox. CONCLUSIONS: The loss of accuracy observed for the formulas at lower values of GFR suggests the mandatory use of gold standards methods as Iohexol Plasma Clearance to assess the correct status of renal function for critical cases. The center 2 showed lower levels of agreement between mGFR and eGFR suggesting that the errors are partially accounted for the Renal Scintigraphy technique too. In particular, we suggest the use of mGFR-iox in oncological urological and nephrological pts with an eGFR lower than 60 mL/min/1.73 m2.

20.
J Surg Oncol ; 121(4): 688-696, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31930511

RESUMO

BACKGROUND: To investigate the effect of frailty on short-term postoperative outcomes and total hospital charges (THCs) in patients with non-metastatic upper urinary tract carcinoma, treated with radical nephroureterectomy (RNU). METHODS: Within the National Inpatient Sample (NIS) database we identified 11 258 RNU patients (2000-2015). We used the Johns Hopkins frailty-indicator to stratify patients according to frailty status. Time trends and multivariable logistic, Poisson and linear regression models were applied. RESULTS: Overall, 1801 (16.0%) patients were frail, 4664 (41.4%) were older than 75 years and 1530 (13.6%) had Charlson comorbidity index ≥2. Rates of frail patients increased over time, from 7.3% to 24.9% (P < .001). Frail patients exhibited higher rates (all P < .05) of overall complications (62.6% vs 50.9%), in-hospital mortality (1.6% vs 1.0%), non-home-based discharge (22.7% vs 12.1%), longer length of stay (LOS) (6 vs 1 day) and higher THCs ($49 539 vs $39 644). Moreover, frailty independently predicted (all P < .05) overall complications (OR, 1.46), in-hospital mortality (OR, 1.52), non-home-based discharge (OR, 1.36), longer LOS (RR, 1.30) and higher THCs (RR, +$11 806). CONCLUSION: Preoperative frailty is important in RNU patients. One of four RNU patients is frail. Moreover, frailty predicts short-term postoperative complications, as well as longer LOS and higher THCs after RNU.


Assuntos
Idoso Fragilizado/estatística & dados numéricos , Nefroureterectomia/estatística & dados numéricos , Neoplasias Urológicas/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Nefroureterectomia/efeitos adversos , Nefroureterectomia/mortalidade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Período Pós-Operatório , Período Pré-Operatório , Neoplasias Urológicas/epidemiologia
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